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Matthias Lorenz

Publications and source records attributed to Matthias Lorenz.

At least 19 recordsLinked to original sources
PubMed2005

Peritransplant immunoadsorption: a strategy enabling transplantation in highly sensitized crossmatch-positive cadaveric kidney allograft recipients.

BACKGROUND: Kidney transplant recipients with a current positive complement-dependent cytotoxicity crossmatch (CDCXM) are at high risk for hyperacute rejection and graft loss. Immunoadsorption (IA) represents an efficient strategy to remove donor-specific alloantibodies. In this analysis, we evaluated effectiveness of peritransplant IA as an anti-humoral strategy to overcome a current positive CDCXM in presensitized renal allograft recipients. METHODS: Between 1999 and 2003, 40 high risk cadaveric kidney allograft recipients (median CDC panel reactive antibody [PRA] level, 77%; number of retransplants, n = 38) were subjected to peritransplant IA with protein A (one pretransplant IA session followed by a course of repeat posttransplant IA sessions) in addition to preemptive antilymphocyte antibody therapy. RESULTS: In nine of these patients, a current positive CDCXM was rendered negative by a single pretransplant IA session. Thirty-one recipients had a negative CDCXM already before pretransplant IA. No difference in graft survival was found between CDCXM-positive and CDCXM-negative recipients (3-year graft survival, 78% vs. 71%, P = 0.6). Comparable rates of immunological graft loss at 3 years were observed (11% vs. 13%, P = 0.8). Patient groups did not significantly differ with respect to median serum creatinine at 1 year (1.23 mg/dL [CDCXM-positive] vs. 1.57 mg/dl [CDCXM-negative], P = 0.07) and at the end of follow-up (median 32 months; 1.19 mg/dL vs. 1.63 mg/dL, P = 0.06). Moreover, patient groups showed similar rates of biopsy-proven cellular rejection (11% vs. 20%) or C4d-positive graft dysfunction (33% vs. 32%). CONCLUSION: Our results demonstrate that peritransplant IA enables successful cadaveric kidney transplantation in the context of a positive CDCXM.

Adult↗
PubMed2005

A silica-based monolithic column in capillary HPLC and CEC coupled with ESI-MS or electrospray-atmospheric-pressure laser ionization-MS.

We describe the successful coupling of CEC and capillary HPLC with the recently developed atmospheric-pressure laser ionization (APLI) method. APLI is suitable for selectively and sensitively ionizing nonpolar aromatic compounds at ambient pressure for subsequent mass-selective detection. The polycyclic aromatic hydrocarbons used as analytes are first separated either by CEC on a silica-based monolithic column or by capillary HPLC. The eluent, along with a sheath flow, is volatilized by microelectrospray and then selectively ionized by excimer laser (KrF*) radiation via two-photon excitation. A QTOF-MS is used as mass-selective detector. This interface combination makes soft ionization of thermally labile nonpolar aromatic analytes possible.

Chromatography, High Pressure Liquid↗
PubMed2005

Iron overload in kidney transplants: prospective analysis of biochemical and genetic markers.

BACKGROUND: The prevalence of iron overload and the influence of mutations in the HFE and TRF2 gene on biochemical markers of iron overload among renal transplant patients is unknown. METHODS: Serum iron, ferritin, transferrin saturation (TSAT), and liver function parameters were analyzed in a cohort of 438 renal transplants. In patients with iron overload, the time course of biochemical markers of iron status as well as the influence of iron loading mutations was investigated during a time period of 5 years. RESULTS: Of 438 renal transplant patients 41 (9.4%) presented with an iron loading phenotype (TSAT above 40% and/or ferritin above 800 ng/mL). Mutations in the HFE gene were present in 12 of 33 (36.3%) patients with iron overload. Among these one patient was homozygous for HFE C282Y, and two patients were compound heterozygous for HFE C282Y/H63D. No individual tested positive for nine other mutations in HFE as well as theTRF2 Y250X mutation. Over time we observed a decrease of mean iron and ferritin levels, and of mean TSAT in our study sample. In patients with mutations in HFE this decrease was less pronounced as compared to patients without mutations. We found an independent positive association between the presence of mutations in HFE and serum alanine-aminotransferase levels at follow-up (P= 0.003). CONCLUSION: Our study demonstrates that iron overload is frequently present in renal transplant patients and shows a continuous decrease over time. This decrease is possibly impaired by the HFE C282Y and HFE H63D mutations. Furthermore, mutations in HFE may influence liver function as reflected by increased alanine-aminotransferase concentrations.

Adult↗
PubMed2004

Risk factors for capillary C4d deposition in kidney allografts: evaluation of a large study cohort.

BACKGROUND: Capillary deposition of the complement split product C4d has turned out to be a valuable marker of antibody-mediated rejection. The impact of pre- and posttransplant variables including particular immunosuppressive regimens on the frequency of C4d deposition has not yet been systematically investigated in a large multivariate analysis. METHODS: In this retrospective study, the authors evaluated the incidence of C4d deposition in 388 kidney transplant recipients subjected to diagnostic biopsy within the first 6 months and analyzed the influence of potential confounders on the rate of C4d-positive graft dysfunction by applying multivariate logistic regression. RESULTS: Sixty-six recipients (17%) developed linear C4d deposits in at least a quarter of peritubular capillaries, a finding associated with inferior 1-year allograft survival (73% vs. 88% in C4d-negative patients, P=0.0003). A 50% reduction in the odds of C4d-positive graft dysfunction was found if calcineurin inhibitor or mycophenolate mofetil (MMF) therapy was started 2 to 4 hr before transplantation when compared with initiation after surgery (adjusted odds ratio [OR], 0.5; P=0.03). No differences with respect to C4d staining results were found for the use of tacrolimus, MMF, or sirolimus, or for cyclosporine C2 monitoring. Retransplantation (OR, 3.6; P<0.001) and presensitization (OR, 3.1; P=0.002) turned out to be strong independent risk factors for C4d deposition. CONCLUSIONS: The authors' results suggest a reduced risk of C4d-positive graft dysfunction for patients receiving immunosuppression before transplantation. Apart from first dose timing, no influence of particular immunosuppressive strategies on C4d staining results was found.

Adult↗
PubMed2004

Refractory Wegener's granulomatosis responds to tumor necrosis factor blockade.

Wegener's granulomatosis is a systemic necrotising vasculitis of small vessels that leads to severe impairment of affected organ systems. Conventional treatment is based on immunosuppression with a combination of steroids, cyclophosphamide, azathioprine or methotrexate over a prolonged time course. Early recurrence or disease refractory to therapy often results in a fatal outcome. As in other inflammatory disorders, tumor necrosis factor (TNF) plays an early and crucial role in progression of disease activity. We report on a patient with severe orbital Wegener's granulomatosis who developed acute renal failure despite intense conventional immunosuppression with cyclophosphamide and steroids. To stop vasculitic activity, by disrupting the autoimmune inflammatory cascade, a TNF-blocking antibody (Infliximab) was administered six times in a six-month period at 3 mg/kg body weight. Conventional immunosuppressive therapy with steroids and cyclophosphamide was continued, the latter being changed to azathioprine after three months. The first infusion of TNF antibody induced improvement of renal function, which continued throughout the course of therapy. The modification of diet in renal disease-glomerular filtration rate (MDRD-GFR) increased from 15.3 ml/min/1.73 m2 before the start of TNF-blockade to 55.5 ml/min/1.73 m2 after six months of therapy. Serum creatinine levels, proteinuria and cANCA titer decreased concomitantly. Clinical remission of Wegener's granulomatosis was induced without any major adverse events. A slight flare of orbital inflammation was successfully treated with an increased dose of azathioprine. Thus, in this case of refractory Wegener's granulomatosis TNF-blockade by monoclonal chimeric TNF-antibody (Infliximab) served as an effective tool to rescue kidney function and induce clinical remission.

Acute Kidney Injury↗
PubMed2004

Percentage of hypochromic red blood cells is an independent risk factor for mortality in kidney transplant recipients.

There are no published studies on the associations between anemia or iron status parameters and important long-term outcomes in kidney transplant recipients (KTR). We prospectively studied 438 KTR from a large transplant clinic for all-cause mortality and kidney allograft loss. Hemoglobin and iron status parameters (serum iron, transferrin, transferrin saturation, ferritin, percentage of hypochromic red blood cells [%HRBC]) were assessed at baseline as were important demographic, clinical and laboratory characteristics. The Austrian Dialysis and Transplant Registry and the Eurotransplant database were used to ascertain immunological and transplantation-related parameters and to ascertain death and allograft rejection. Cox proportional hazard models were used for analyses. Over 7.8 years of follow-up, 129 deaths (29.5%) occurred and 208 grafts (47.5%) were lost. From multivariate analyses, we found that anemia (hemoglobin <10g/dL) was not associated with mortality or graft loss. Among the iron status parameters, only %HRBC was associated with greater all-cause mortality. Patients with HRBC >10% had twice the mortality risk (HR: 2.06; 95%CI: 1.12-3.79) compared to patients with HRBC <5%. Neither of the iron status parameters were associated with allograft rejection. In conclusion, we found that %HRBC was an independent risk factor for mortality in KTR, while other iron status parameters or anemia were not associated with risk. Larger studies on the association between anemia and these outcomes are warranted.

Anemia, Hypochromic↗
PubMed2004

The effect of ACE inhibitor and angiotensin II blocker therapy on early posttransplant kidney graft function.

BACKGROUND: It is unknown whether continuation of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II (ATII) blocker therapy after kidney transplantation has an influence on early kidney graft function. METHODS: We compared early postoperative graft function between 260 cadaveric kidney transplant recipients, either with or without peritransplantation ACE inhibitor/ATII blocker therapy. Regression analysis was used to show the influence of variables interfering with posttransplantation serum creatinine levels. The effect of different variables on the occurrence of delayed graft function (DGF) was analyzed by means of stepwise logistic regression. Improvement in kidney function during the first week after transplantation was compared between groups by means of Kaplan-Meier survival analysis. RESULTS: Intake of an ACE inhibitor or ATII blocker did not influence immediate posttransplantation graft function or the occurrence of DGF. Conversely, serum creatinine levels decreased significantly faster in patients administered an ACE inhibitor/ATII blocker than in those without therapy (P < 0.01). The only variables delaying graft function were number of previous transplantations, cold ischemia time, and male sex. Among patients with DGF, those with ACE inhibitor/ATII blocker therapy had significantly faster graft recovery (P < 0.001). CONCLUSION: Our results suggest that intake of an ACE inhibitor or ATII blocker during the immediate posttransplantation course is safe and does not impair graft function. Additionally, patients with DGF might profit from blockade of the renin-angiotensin-aldosterone system, which possibly shortens the time to graft recovery.

Angiotensin II↗
PubMed2004

Ferrous sulfate does not affect mycophenolic acid pharmacokinetics in kidney transplant patients.

BACKGROUND: Oral administration of ferrous-sulfate was reported to decrease intestinal absorption of mycophenolate mofetil (MMF) in healthy Japanese individuals by 90%. METHODS: We examined the effect of a single oral dose of ferrous sulfate on steady-state mycophenolic acid pharmacokinetics in 10 iron-deficient (hypochromic red blood cells >2.5%), Caucasian, long-term kidney graft recipients using a randomized, open-label, crossover design. On days A and B, MMF (1,000 mg) was given orally at 8:00 am. On day C, MMF and ferrous sulfate (105 mg) were coadministered at 8:00 am. On day D, MMF was given at 8:00 am and ferrous sulfate was given orally 4 hours later. RESULTS: The interindividual variability of the 12-hour area under the plasma mycophenolic acid concentration versus time curves (AUC(0-12)) under control conditions was small (89.5 +/- 27.8 and 87.6 +/- 39.1 mg x h/L, respectively). Concomitant or subsequent administration of MMF and ferrous sulfate did not affect the bioavailabilty of MMF (AUC(0-12), 91.9 +/- 30.4 mg x h/L and 96.0 +/- 31.7 mg x h/L). CONCLUSION: Oral therapy of iron deficiency using ferrous sulfate in long-term kidney graft recipients does not impede intestinal absorption of MMF; hence, exposure to this immunosuppressive agent is not reduced.

Administration, Oral↗
PubMed2004

Results of a nationwide screening for Anderson-Fabry disease among dialysis patients.

Anderson-Fabry disease is possibly underdiagnosed in patients with end-stage renal disease. Nationwide screening was therefore undertaken for Anderson-Fabry disease among dialysis patients in Austria. Screening for alpha-galactosidase A (AGAL) deficiency was performed by a blood spot test. In patients with a positive screening test, AGAL activity in leukocytes was determined. Individuals with decreased leukocyte AGAL activity were subjected to mutation testing in the GLA gene. Fifty (90.9%) of 55 Austrian hemodialysis centers participated in this study; 2480 dialysis patients (80.1% of the Austrian dialysis population) were screened. In 85 patients, the screening test was positive (85 of 2480, 3.42%; women, 3.32%; men, 3.50%). Among these 85 patients, 4 men (in 3 of whom Anderson-Fabry disease was already known before screening) had a severely decreased and 11 subjects had a borderline low AGAL activity. Genetic testing revealed mutations associated with Fabry disease in all four men with severely decreased AGAL activity resulting in a prevalence of 0.161% for the entire study population. A nationwide screening of dialysis patients permitted detection of a hitherto unknown man with Anderson-Fabry disease. The overall prevalence among dialysis patients was at least ten times higher as compared with recent registry data. Screening programs among patients with end-stage renal disease, especially men, should be put in place to identify families with Anderson-Fabry disease who probably may benefit from specific clinical care, and perhaps from enzyme replacement therapy. In dialysis patients, however, there is no evidence to support enzyme replacement therapy at present.

Aged↗
PubMed2004

C-reactive protein and body mass index independently predict mortality in kidney transplant recipients.

C-reactive protein (CRP) is a risk factor for cardiovascular outcomes and mortality in the general population. To date, there are no prospective studies of the association between CRP and mortality or allograft loss in kidney transplant recipients (KTR). In 1995, 438 consecutive KTR were enrolled in this prospective study. Important information on demographic, clinical and immunological characteristics was collected at baseline, and CRP was measured using standard methods. Patients were then followed-up for a median 7.8 years. Time-to-event analyses (univariate and multivariate Cox proportional hazards regression models) were used to study the main outcomes: all-cause mortality and kidney allograft loss, defined as the earlier of return to dialysis, re-transplantation, or death. From univariate analyses, we found that CRP >or=0.5 mg/dL was associated with a 83% greater mortality risk compared with lower levels of this inflammatory marker [hazard ratio (HR) = 1.83; 95% confidence interval (CI): 1.23-2.72; p = 0.003]. After multivariate adjustment, patients with a CRP >or=0.5 mg/dL had a 53% higher mortality risk compared with patients whose CRP was below that threshold (HR = 1.53; 95% CI: 1.01-2.31; p = 0.04). No associations between CRP and the risk of kidney allograft loss were detected. Furthermore, we were not able to detect any effect modification between CRP and body mass index on the outcomes under study. We conclude that CRP predicts all-cause mortality, but not allograft loss in stable KTR.

Adult↗
PubMed2003

Anderson-Fabry disease in Austria.

Fabry disease is an X-linked inherited inborn error of glycosphingolipid catabolism. The deficiency of alpha-galactosidase A leads to the deposition of glycosphingolipids primarily in lysosomes of blood vessel cells. In classically affected hemizygotes clinical manifestations include pain in the extremities, vessel ectasia (angiokeratoma) in skin and mucous membranes, ophthalmological abnormalities, and hypohidrosis. As disease progresses there is renal, cardiac, cerebral and vascular involvement, with most patients experiencing renal insufficiency, cardiac hypertrophy or stroke. Many female carriers of Fabry disease also have symptoms. Recently available enzyme replacement therapy has the potential to control or even reverse disease progression. The present analysis reports on five Austrian families with Fabry disease, cared for by nephrologists in June 2002. Furthermore we discuss potential indications for enzyme replacement therapy in patients maintained on renal replacement therapy.

Adult↗
PubMed2003

Multigene analysis of Rb pathway and apoptosis control in esophageal squamous cell carcinoma identifies patients with good prognosis.

Deregulation of cell-cycle G(1)-restriction point control by disruption of Rb-pathway components is a frequent event in cancer. In concert with the inactivation of cell death pathways, such events not only contribute to tumor development but also determine the intrinsic and acquired resistance to cancer therapy and, ultimately, disease prognosis. We previously observed that the cyclin-dependent kinase inhibitor p16(INK4a) and the proapoptotic Bcl-2 homolog Bax are positive prognostic factors and identify patients with good prognosis in esophageal squamous cell carcinoma (SCC). In the present study, we therefore extend our analysis to additional genes controlling the G(1) restriction point and apoptosis, respectively. This retrospective analysis was performed in a cohort of 53 patients undergoing surgery for esophageal SCC with curative intent, i.e., R0 resection. Protein expression profiles of cyclin D1, p16(INK4a), Rb, p21(CIP/WAF-1), p53, Bax and Bcl-2 were analyzed by immunohistochemistry and compared to p53 mutational status, as determined by SSCP-PCR of exons 5-8. Loss of p16(INK4a), Rb, p21(CIP/WAF-1) or Bax and overexpression of cyclin D1 were associated individually with shorter overall survival, while Bcl-2 expression and p53 mutation were not of prognostic relevance. The longest survival was observed in a subgroup of patients whose tumors bore a combination of favorite genotypes, i.e., low cyclin D1 and high Rb, p21(CIP/WAF-1), p16(INK4a) and Bax protein expression. These results show that multigene analyses based on limited sets of functionally linked genes reliably identify patients with good vs. poor prognosis.

Adult↗
PubMed2003

Flow monitoring: performance characteristics of ultrasound dilution versus color Doppler ultrasound compared with fistulography.

BACKGROUND: Measurement of access blood flow is the preferred noninvasive screening test for hemodialysis arteriovenous (AV) fistula stenosis. However, performance characteristics of the 2 most frequently used ultrasound techniques compared with fistulography remain elusive. METHODS: We evaluated 59 hemodialysis patients with native forearm AV fistulae who underwent all 3 measurements in a prospective order: the ultrasound dilution technique (UDT), color Doppler ultrasonography (CDUS), and fistulography. Patients with angiographically diagnosed access stenosis underwent angioplasty and were followed up by means of monthly UDT measurements until restenosis occurred within the first 6 months. RESULTS: Both ultrasound techniques predicted access stenosis (P < 0.01). Performance was similar between both techniques, evaluated by receiver operating characteristic curves. Areas under the curve averaged 0.79 (95% confidence interval [CI], 0.66 to 0.91) for UDT and 0.80 (95% CI, 0.65 to 0.94) for CDUS. Correlation between measured UDT and CDUS blood flow rates was 0.37 (Spearman's rho, rho = 0.004). The calculated optimal cutoff value for the prediction of stenosis was 465 mL/min for the UDT and 390 mL/min for the CDUS technique. Access stenosis was diagnosed in 41 patients who subsequently underwent percutaneous angioplasty (PTA), which was successful in 34 patients. Restenosis occurred in 13 patients within the first 6 months after PTA. UDT access blood flow after PTA was significantly lower in these 13 patients compared with the other 21 patients. CONCLUSION: Our data suggest that blood flow monitoring of AV hemodialysis access by ultrasound provides a reasonable prediction of access stenosis and restenosis.

Adult↗
PubMed2003

Prospective pilot study of neoadjuvant chemotherapy with 5-fluorouracil, folinic acid and oxaliplatin in resectable liver metastases of colorectal cancer. Analysis of 42 neoadjuvant chemotherapies.

PURPOSE: Since there are currently no data available from a prospective trial, the primary objective of this prospective study was to investigate whether the rate of R0-liver resections without morbidity would be at least 50 % in patients with neoadjuvant chemotherapy for colorectal liver metastases. PATIENTS AND METHODS: 42 patients were treated with a biweekly FOLFOX regimen. Chemotherapy consisted of a 2-hour infusion of folinic acid (FOL) 500 mg/m2, followed by a 24-hour infusion of 5- fluorouracil (F) 2000 mg/m2 daily for two days. Oxaliplatin (OX) 85 mg/m 2 was given simultaneously with FOL. Treatment allocation was randomized with either 3 or 6 cycles for the final 30 patients. A liver resection was performed 2 to 5 weeks after the final infusion. RESULTS: An objective response was observed in 20 of 42 patients (response rate was 27 % higher after 6 cycles). Liver resection (R0) could be performed in 34 patients. Postoperative complications were reported in 14 patients (13 occurring within 30 days after resection) and severe complications in 5 cases (including two deaths after extended resection). Liver failure and persistent biliary fistula were the most frequently documented complications. There was no relevant difference in safety criteria between 3 and 6 applications. CONCLUSION: The use of neoadjuvant chemotherapy in resectable liver metastases induced significant remissions without increasing morbidity. The rate of severe complications and cases of no R0-resection in this study was 31 % and was with that significantly lower than 50 % (95 % CI 17.6 %-47.1 %). The risk to the patient is therefore acceptable when undergoing neoadjuvant treatment in a prospective intergroup trial.

Adult↗
PubMed2003

Technical complications of continuous intra-arterial chemotherapy with 5-fluorodeoxyuridine and 5-fluorouracil for colorectal liver metastases.

BACKGROUND: Intra-arterial chemotherapy is an effective modality to treat unresectable hepatic metastases from colorectal primaries if systemic chemotherapy has failed. Response rates of more than 40% and a median survival of 15 to 25 months have been reported from randomized trials. In this retrospective study, we analyzed specific technical complications associated with continuous intra-arterial chemotherapy for colorectal liver metastases. METHODS: From 1982 to 1995, single-center clinical data from 180 patients with colorectal liver metastases were evaluated. Continuous intra-arterial chemotherapy was administered using either an implanted infusion pump or an intra-arterial port with an external infusion pump. The intra-arterial catheter was implanted according to the Watkins' technique. The treatment protocols consisted of 5-fluorouracil- or 5-fluorodeoxyuridine-based regimens. RESULTS: A total of 70 patients (39%) received an intra-arterial infusion pump and 110 patients (61%) an intra-arterial port. Sixty-eight technical complications affected port systems (62%), whereas 29 patients with pumps (41%) were affected by technical complications. Therapy-relevant complications were observed in 47% of the ports and 30% of the infusion pumps. The median complication-free survival was 12.2 months for infusion pumps and 7.3 months for ports (P =.0016). CONCLUSIONS: Our data demonstrate that pumps are superior to ports in terms of complication rate and complication-free survival. On the basis of our results, pumps have a potential for a longer treatment, which may result in a prolonged median survival.

Antimetabolites, Antineoplastic↗
PubMed2002

Regional chemotherapy.

Regional chemotherapy is an interesting treatment option in patients with advanced pancreatic cancer but cannot be considered standard treatment, and it should not be performed outside controlled clinical trials. The real value of regional chemotherapy must be evaluated in larger, randomized trials. New drug combinations may reduce the observed side effects and improve tumor response. Gene therapy with p53 and K-ras modulated herpesviruses may become a palliative treatment option and can be administered easily by regional chemotherapy techniques [23].

Adenocarcinoma↗